Assay information management methods and devices

ABSTRACT

The present invention relates to methods, devices and systems for associating assay information with an assay consumable used in a biological assay. Provided are assay systems and associated consumables, wherein the assay system includes a reader adapted to read/erase/write information from/to an assay consumable identifier associated with the assay consumable. Various types of assay information are described, as well as methods of using such information in the conduct of an assay by an assay system.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of copending U.S. patent applicationSer. No. 12/844,345, filed Jul. 27, 2010, which claims the benefit ofU.S. Provisional Application No. 61/271,873 filed Jul. 27, 2009, theentire contents of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present teaching relates to methods, devices and systems forassociating assay information with an assay consumable used in abiological assay.

BACKGROUND OF THE INVENTION

Numerous methods and systems have been developed for conducting assays.These methods and systems are essential in a variety of applicationsincluding medical diagnostics, veterinary testing, food and beveragetesting, environmental monitoring, manufacturing quality control, drugdiscovery, and basic scientific research. During the manufacture and useof reagents and other consumables used in biological assays, thereagents and consumables are typically coded and labeled by themanufacturer in order to track them. In addition, a myriad of analyticalparameters must be tracked in order to understand the analytical resultsof any given assay, often requiring input from various parallel trackingsystems supplied by the manufacturer, user or both.

SUMMARY OF THE INVENTION

The present invention provides an assay system configured to use anassay consumable in the conduct of an assay, said assay systemcomprising a reader adapted to perform an operation selected from thegroup consisting of (i) reading information from an assay consumableidentifier associated with said assay consumable; (ii) erasinginformation from said assay consumable identifier; (iii) writinginformation to said assay consumable identifier; and (vi) combinationsthereof. In one embodiment, the information is used by said system toadjust one or more operations performed by said system before, duringand/or after the conduct of an assay by said system.

In a specific embodiment, the information comprises information used toidentify an element selected from the group consisting of (i) said assayconsumable, (ii) one or more test sites within said consumable, (iii) areagent and/or sample that has been or will be used in said consumable,and (iv) combinations thereof. For example, the information is used todistinguish a first test site within said consumable from a differenttest site within said consumable. In one embodiment, the information isconsumable information selected from the group consisting of lotidentification information; lot specific analysis parameters,manufacturing process information, raw materials information, expirationdate; calibration data; threshold information; the location ofindividual assay reagents and/or samples within one or more test sitesof the assay consumable; Material Safety Data Sheet (MSDS) information,and combinations thereof.

The information may also be sample information selected from the groupconsisting of the location of samples within said at least one testsites of the assay consumable; assay results obtained on said assayconsumable for said sample; identity of samples that have been and/orwill be assayed in said assay consumable; and combinations thereof. Theinformation may include chain of custody information, e.g., informationregarding the control, transfer and/or analysis of said sample. Thechain of custody information may include information concerning thecontrol, transfer and/or manufacture of said assay consumable, includingbut not limited to user identification; time and date stamp for saidassay; location of said assay system during said assay; calibration andQC status of said assay system during said assay, custody and/orlocation information for said assay consumable before and after theconduct of said assay; assay results for said sample; and combinationsthereof. Still further, the information is chain of custody informationselected from the group consisting of time, date, manufacturingpersonnel or processing parameters for one or more steps during themanufacture of said assay consumable; custody, location and or storageconditions for said assay consumable following manufacture and/orbetweens steps during the manufacture of said assay consumable; andcombinations thereof.

In another embodiment, the information is consumable/test siteinformation selected from the group consisting of consumable type andstructure; location and identity of assay reagents included with saidassay consumable; location and identity of assay reagents within anassay test site of said assay consumable; and combinations thereof.

Alternatively, the information is assay process information selectedfrom the group consisting of assay parameters to be applied by saidreader during the assay; a sequence of steps to be applied by saidreader during said assay; the identity, concentration, and/or quantityof assay reagents to be used or added during said assay; the type orwavelength of light to be applied and/or measured by the reader duringsaid assay; the temperature to be applied by the reader during saidassay; an incubation time for said assay; statistical or analyticalmethods to be applied by the reader to raw data collected during saidassay; and combinations thereof. In a further embodiment, the assay is amulti-step assay and said assay process information relates to a step orstep(s) of said multi-step assay.

Still further, the consumable/test site information comprisesinformation concerning assays previously performed by a reader on one ormore test sites of said consumable; information concerning assays to beperformed by an assay reader or a component thereof on one or more testsites within said consumable; and combinations thereof.

The information may further include consumable security informationselected from the group consisting of information concerning assayconsumable authentication; information concerning appropriate placementand/or orientation of said assay consumable in said system; informationconcerning defects in said assay consumable and/or a test site thereof;and combinations thereof.

The information may be used by said system to adjust the operation of acomponent of said assay system selected from the group consisting of oneor more sensors; mechanisms to transport the assay consumables into andout of the system; mechanisms to align and orient the assay consumableswith said one or more sensors and/or with electrical, mechanical orfluidic interfaces in said system; mechanisms, electronics or softwareto track and/or identify assay consumables; mechanisms to store, stack,move and/or distribute one or more consumables.

The invention further provides an assay system configured to use anassay consumable in the conduct of an assay comprising a reader adaptedto perform an operation selected from the group consisting of (i)reading information from an assay consumable identifier associated withsaid assay consumable; (ii) erasing information from said assayconsumable identifier; (iii) writing information to said assayconsumable identifier; and (iv) combinations thereof; wherein saidinformation comprises consumable/test site information selected from thegroup consisting of information concerning assays previously performedby a reader on one or more test sites of said consumable; informationconcerning assays to be performed by an assay reader or a componentthereof on one or more test sites within said consumable; andcombinations thereof.

The invention also provides an assay system configured to use an assayconsumable in the conduct of an assay comprising a reader adapted toperform an operation selected from the group consisting of (i) readinginformation from an assay consumable identifier associated with saidassay consumable; (ii) erasing information from said assay consumableidentifier; (iii) writing information to said assay consumableidentifier; and (iv) combinations thereof; wherein said informationcomprises consumable security information selected from the groupconsisting of information concerning assay consumable authentication;information concerning appropriate placement and/or orientation of saidassay consumable in said system; information concerning defects in saidassay consumable and/or a test site thereof; and combinations thereof.

Still further, the invention contemplates an assay system configured touse a multiplex enabled assay consumable in the conduct of a multiplexedassay, wherein said assay consumable comprises a plurality of test siteswithin which said multiplexed assay is performed and said assay systemcomprises a reader adapted to perform an operation selected from thegroup consisting of (i) reading information from an assay consumableidentifier associated with said assay consumable; (ii) erasinginformation from said assay consumable identifier; (iii) writinginformation to said assay consumable identifier; and (iv) combinationsthereof.

The invention also provides an assay consumable comprising an assayconsumable identifier comprising information, wherein said assayconsumable is selected from the group consisting of (i) an assayconsumable comprising at least one assay test site for said assay; and(ii) a container adapted to hold one or more assay reagents.

In one embodiment, the invention provides a multiplex enabled assayconsumable comprising (i) a plurality of test sites for an assay,wherein each of said test sites comprise a plurality of distinct assaydomains, each of said domains comprising reagents for measuring adifferent analyte; and (ii) an assay consumable identifier comprisinginformation used to identify an element selected from the groupconsisting of (i) said assay consumable, (ii) one or more test siteswithin said consumable, (iii) a reagent and/or sample that has been orwill be used in said consumable, and (iv) combinations thereof.

The invention also contemplates a method of using an assay consumable inan assay system, wherein said assay consumable comprises a consumableidentifier and said assay system comprises a reader adapted to performan operation selected from the group consisting of (i) read informationfrom said consumable identifier; (ii) erase information from saidconsumable identifier; (iii) write information to said consumableidentifier; and (iv) combinations thereof, said method comprising thesteps of (a) reading information from said consumable identifier; (b)conducting an assay in said assay system using said assay consumable;and (c) writing information resulting from said assay conducted in step(b) to said consumable identifier.

Still further, the invention provides a method of using an assayconsumable in an assay system, wherein said assay consumable comprises aconsumable identifier and said assay system comprises a reader adaptedto perform an operation selected from the group consisting of (i) readinformation from said consumable identifier; (ii) erase information fromsaid consumable identifier; (iii) write information to said consumableidentifier; and (iv) combinations thereof, said method comprising thesteps of (a) reading information from said consumable identifier;(b)conducting an assay in said assay system using said assay consumable;(c) writing information resulting from said assay conducted in step (b)to said consumable identifier; and (d) tracking use of said assayconsumable.

In one embodiment, the invention provides a method of tracking use of anassay consumable comprising an assay consumable identifier and aplurality of test sites, said method comprising (a) reading test siteusage information from said assay consumable identifier; (b)identifying, based on said test site usage information, an availabletest site on said consumable; (c) carrying out an assay using saidavailable test site; and (d) writing updated test site usage informationto said assay identifier.

Moreover, the invention provides a method of tracking the manufacture ofan assay consumable, wherein said assay consumable comprises anidentifier and one or more component parts and said manufacturingprocess includes one or more operations conducted by one or moremanufacturing consumables each comprising a reader adapted to perform anoperation selected from the group consisting of (i) readingmanufacturing information from said identifier; (ii) erasingmanufacturing information from said identifier; (iii) writingmanufacturing information to said identifier; and (iv) combinationsthereof; said method comprising (a) affixing said identifier to a firstcomponent of said consumable; (b) performing an operation of saidmanufacturing process; (c) writing manufacturing information to saididentifier, wherein said manufacturing information comprises informationrelated to the operation performed in step (b); (d) performing anadditional step in said manufacturing process; and (e) writingmanufacturing information to said identifier, wherein said manufacturinginformation comprises information related to the operation performed instep (d).

Also provided is an assay system configured to use an assay cartridge inthe conduct of an assay, said assay system comprising a reader adaptedto perform the following operations (i) reading cartridge lotidentification information from a first consumable identifier associatedwith said assay consumable; (ii) reading lot specific parameters from anadditional consumable identifier; (iii) using said lot identificationinformation and said lot specific parameters to adjust one or moreoperations performed by said assay system before, during and/or afterthe conduct of an assay by said system. The lot specific parameters maybe selected from the group consisting of (i) a revision level thatdetermines schema used to interpret assay results and/or assayinformation; (ii) cartridge type; (iii) year of cartridge manufacture;(iv) cartridge lot number; (v) expiration date of cartridge and/orreagents used in said assay; (vi) a cross-talk correction matrix toaccount for chemical cross-reactivity; (vi) threshold values for assaysto be conducted in said cartridge; (vii) a range for internal positivecontrol(s) used in said assay; (viii) a ranges for each assay to beconducted in said cartridge for a positive control.

Still further, the invention provides an assay system configured to usea multi-well assay plate, an additional multi-well assay plate, and oneor more sample tube racks in the conduct of an assay, said assay systemcomprising a reader adapted to perform the following operations (i)reading tube position information from a first consumable identifierassociated with said one or more sample tube racks; (ii) reading assayinformation and lot specific parameters from an additional consumableidentifier associated with said additional multi-well assay plate; (iii)using position information and said lot specific parameters to adjustone or more operations performed by said assay system before, duringand/or after the conduct of an assay on said multi-well assay plate bysaid system; (iv) erasing information from said additional consumableidentifier; and (v) writing information to said additional consumableidentifier.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

Unless otherwise defined herein, scientific and technical terms used inconnection with the present invention shall have the meanings that arecommonly understood by those of ordinary skill in the art. Further,unless otherwise required by context, singular terms shall includepluralities and plural terms shall include the singular. The articles“a” and “an” are used herein to refer to one or to more than one (i.e.,to at least one) of the grammatical object of the article. By way ofexample, “an element” means one element or more than one element.

The assay consumables and systems of the present invention include avariety of devices and configurations. In one embodiment, the assaysystem of the present invention includes an assay reader capable ofconducting a biological assay using an assay consumable. The assayconsumable comprises an identifier (referred to alternatively throughoutthe specification as an identifier, a consumable identifier, or an assayconsumable identifier) and the assay system, reader or a componentthereof comprises an identifier controller that interacts with theidentifier. As described hereinbelow, the identifier includesinformation concerning the assay consumable, which may include but isnot limited to, how the consumable is manufactured and handled prior touse and how the consumable is used in an assay system. Therefore, theassay system is configured to use an assay consumable in the conduct ofan assay, and the assay system includes a reader adapted to perform anoperation selected from (i) reading information from an assay consumableidentifier associated with the assay consumable; (ii) erasinginformation from the assay consumable identifier; and/or (iii) writinginformation to the assay consumable identifier. The information may beused by the system to perform a variety of operations, e.g., to performany aspect of a biological assay, tracking the use and/or performance ofthe assay consumable and/or the assay system, associating particularinformation unique to that assay consumable with that consumable so thatthe information may be accessed and used in subsequent applications inthe same or a different assay system, and/or to adjust one or moreoperations performed by the system before, during and/or after theconduct of an assay by the system.

The assay systems contemplated by the present invention are used toconduct any type of diagnostic or analytical method known in the art.Such analytical methods include but are not limited to clinicalchemistry assays (e.g., measurements of pH, ions, gases andmetabolites), hematological measurements, nucleic acid amplificationassays (e.g., polymerase chain reaction (PCR) and ligase chain reactionassays), immunoassays (e.g., direct, sandwich and/or competitiveimmunoassays and serological assays), oligonucleotide ligation assays,and nucleic acid hybridization assays. Any biological reagent that mightbe used in such analytical methods may be used in such systems,including but not limited to nucleic acids, nucleotides,oligonucleotides, DNA, RNA, PNA, primers, probes, antibodies orfragments thereof, antigens, small molecules, e.g., drugs or prodrugs,streptavidin, avidin, and biotin.

These systems may be portable, e.g., hand-held, and/or operated within afixed laboratory or field setting, alone or in combination with one ormore additional components, assay devices or systems. These systems maybe used in a variety of applications, from field operations tolaboratory settings, in a wide variety of industries, including but notlimited to, medical, clinical, forensic, pharmaceutical, environmental,veterinary, biological, chemical, agricultural, waste management,hazardous chemical, drug testing, and in defense applications, e.g., forthe detection of biological warfare agents. The assay systems andconsumables used in the present invention may detect an analyte ofinterest by any suitable method, including but not limited to, optical,electromechanical, radiowave, electromagnetic, colorimetric,fluorimetric, chemiluminescent, electrochemiluminescent, radiochemical,nuclear magnetic resonance, enzymatic, fluorescent, particle-count, andcell-count based detection.

The assay consumable includes devices in which one or more steps of anassay process are conducted and such devices may include one or moretest sites where an assay measurement is conducted. In one embodiment,the assay consumable includes at least one assay test site for an assay.A test site may include a plurality of distinct assay domains, at leasttwo of the domains including reagents for measuring different analytes.Still further, the consumable may include a plurality of test sites fora plurality of individual assays. Alternatively, the assay consumablemay be a component that provides a reagent or other assay component thatis used by the system to conduct an assay. For example, the assayconsumable may be a container with one or more compartments for holdingassay reagents. The assay consumable (or test sites therein) may besingle use or it may be reusable. The assay consumable may be configuredto conduct one test or multiple tests (sequentially or in parallel).

Test sites, as used herein, refer to regions of a consumable that hold,contact and/or interrogate a sample. A test site may include a pluralityof distinct assay domains, at least two such domains include reagentsfor measuring different analytes. Consumables may comprise multiple testsites which may hold, contact or otherwise interrogate distinct volumes(aliquots) of the same sample and/or volumes of different samples. Asector of an assay consumable refers to grouping of two or more testsites of the consumable. Each test site may be used to conduct a singlemeasurement or multiple measurements on a volume of sample (for example,the measurement of multiple different analytes in a multiplexed assayformat). Depending on the specific requirements of an application, aconsumable with multiple test sites may be configured to use all of itstest sites in parallel, to use its test sites at different times (e.g.,assigning unused test sites to be used as new samples are delivered tothe assay system), or a combination of both modes of operation may beenabled.

The assay consumable may be any structure useful in diagnosticapplications and that structure may be dictated by the particular assayformat or detection method employed by the device. Examples of assayconsumables suitable for use with the invention include, but are notlimited to, test tubes, cuvettes, flow cells, assay cartridges andcassettes (which may include integrated fluidics for assay processing),multi-well plates, slides, assay chips, lateral flow devices (e.g.,strip tests), flow-through devices (e.g., dot blots), pipette tips,solid phase supports for biological reagents and the like. In certainembodiments, test sites in the assay consumable are defined bycompartments in the assay consumable, e.g., wells, chambers, channels,flow cells and the like. The assay consumable and/or test sites mayinclude one or more components used to carry out an assay measurementaccording to one or more specific detection methodologies. Depending onthe function of the consumable and the detection modalities employed bythe assays system, examples of such components may include, but are notlimited to, lateral flow matrices, filtration matrices, optical windows,sensors (e.g., electrochemical and optical sensors), solid phasesupports for binding reactions (e.g., coated slides, chips, beads, pins,coated filtration or lateral flow matrices, tubes and the like),reagents (dry or in liquid form), electrodes, analyte selectivemembranes and the like.

In one embodiment, the assay consumable may be a device thatincorporates a conventional lateral flow test strip, e.g., animmunoassay test strip, as an assay medium. In this example, the deviceis molded to include an identifier or the identifier is affixed to thedevice without any modification to the structure of the device and/orthe assay medium. In one embodiment, the device is placed within theanalytical system, i.e., the assay system, for analysis and before,during or after the performance of the assay, the identifier controllerwithin, affixed to or associated with the assay system reads the datacontained on the identifier and uses that data in the assay or after theassay is completed by the system.

In another embodiment, the assay consumable and accompanying assaysystem or reader is capable of performing a multiplex assay. A multiplexassay is a type of assay in which multiple measurements are performed ona single sample, e.g., by distributing samples across multiple testsites and/or by carrying out multiple measurements on volumes of samplesin individual test sites. The multiple measurements may include, but arenot limited to, (i) multiple replicates of a measurement for an analyte;(ii) multiple measurements of a certain analyte (i.e., multiplenon-identical measurements for the same analyte, e.g., measurements thatdiffer in format or in the identity of the assay reagents that areemployed); and/or (iii) measurements of multiple different analytes. Inone specific embodiment, an assay consumable is configured to carry out,in one or more test sites, multiplex measurements that include at leasttwo assays for two different analytes.

The invention is not restricted to specific approaches for conductingmultiplex measurements in a test site and may employ any of the numeroustechniques that have been developed for carrying out multiplexmeasurements. Multiplex measurements that can be used with the inventioninclude, but are not limited to, multiplex measurements (i) that involvethe use of multiple sensors; (ii) that use discrete assay domains on asurface (e.g., an array) that are distinguishable based on location onthe surface; (iii) that involve the use of reagents coated on particlesthat are distinguishable based on a particle property, such as size,shape, color, etc.; (iv) that produce assay signals that aredistinguishable based on optical properties (e.g., absorbance oremission spectrum), (v) that are based on temporal properties of anassay signal (e.g., time, frequency or phase of a signal), and/or (vi)that are based on some other assay characteristic. Accordingly,interpretation of multiplexed assay results may involve the use ofmultiplexing information, such as the identity of the assays carried outin each test site and, within a test site, any assay characteristics(identity of specific sensors, location and identity of assay domains,etc.) that are used to distinguish assays carried out in a test siteand/or that are used to tie a specific assay identity to thecorresponding assay signal.

In one embodiment, an assay test site comprises a plurality of distinctassay domains and each domain comprises one or more reagents formeasuring a different analyte. Multiplexing information, including thelocation, identity, and composition of each assay domain, is used toidentify the assay signal generated at each domain and connect it to adetermination of the presence or amount of the corresponding analyte (aprocess which may include the application of additional assayinformation such as signal thresholds and/or calibration parameters).

A test site may be configured to carry out a plurality of multiplexedmeasurements (e.g., it may include a plurality of distinct assaydomains, wherein each domain comprises reagents for measuring adifferent analyte). In one embodiment, the assay consumable may includea plurality of test sites. Information regarding the exact configurationof the one or more test sites, assay domains, and/or one or more sectorsin a consumable may be included in the information saved to the assayconsumable identifier. This information may include the location andidentity of the test sites, assay domains, and/or one or more sectors aswell as multiplexing information (as described above) including thenumber, identity and differentiating characteristics of the individualmeasurements within a test site, assay domain, and/or sector (e.g., thespecific locations, identities and/or assay reagents of assay domainswithin each test site). In addition, the use of a test site, assaydomain, and/or sector in an assay consumable may also be recorded to theidentifier to track the use of the consumable in an assay system. Theidentifier may also include information concerning the assay format andspecific processing steps to be used for an assay consumable or testsite, assay domain, and/or sector of an assay consumable. The identifiermay also include information concerning analytical methods that shouldbe applied by the system once an assay is conducted to analyze theoutput of an assay in a given test site, assay domain, and/or sectorand, optionally, to provide results that combine the output frommultiple assays in a test site, assay domain, and/or sectors.

The test sites may be configured in any suitable configuration,depending on the geometry of the consumable and/or the type of assayconducted with the consumable. In one embodiment, the test sites areconfigured as wells and/or chambers in the assay consumable. Forexample, the assay consumable of the present invention may be amulti-well plate (e.g., a 24-, 96-, 384- or 1536-well plate), and thewells of the plate can further comprise a plurality (e.g., 2 or more, 4or more, 7 or more, 25 or more, 64 or more, 100 or more, etc.) ofdistinct assay domains. Multi-domain multi-well plates that are adaptedto allow assay measurements to be conducted using electrode inducedluminescence measurements (e.g., electrochemiluminescence measurements)are described in U.S. application Ser. No. 10/238,391, entitled “Methodsand Reader for Conducting Multiple Measurements on a Sample”, filed onSep. 10, 2002, hereby incorporated by reference. The exact configurationof the domains, test sites, and/or sectors in an assay consumable, aswell as the specific identity of each domain, test site, and/or sectorand the reagents bound to that domain/test site/sector may be includedin the information saved to the assay consumable identifier. Inaddition, the use of a given domain, test site, and/or sector in anassay consumable may also be recorded to the identifier to track the useof the consumable in an assay system.

Assay consumables can be used in a plurality of diverse assays and thisdiversity leads to a variety of suitable configurations of theassociated consumable. In one assay format, the same analyte is measuredat different assay domains within a test site, the different assaydomains being designed to measure a different property or activity ofthe analyte. Information concerning the assay format that may be used inan assay consumable, test site and/or assay domain may also be saved tothe assay consumable identifier. The identifier may also includeinformation concerning analytical methods that should be applied by thesystem once an assay is conducted to analyze the output of an assay in agiven test site and/or domain and compare that output to an assay in aseparate test site and/or domain.

One example of a multiplex assay consumable and reader is described inU.S. 2004/0022677, the disclosure of which is incorporated herein byreference in its entirety. Such assay consumables include one or more,and in one embodiment, a plurality of test sites and/or assay domainsfor conducting one or more assay measurements simultaneously orsequentially. For example, the test sites may be configured as wellsand/or chambers. These test sites and/or assay domains comprise one ormore electrodes for inducing luminescence from materials in the testsites and/or assay domains. The assay consumables may further compriseassay reagents in liquid or dry form, e.g., in the test sites, e.g.,wells or chambers, of the consumable.

In addition to the test sites and assay domains, an assay consumable ormulti-well assay plate may include several additional elements, e.g., aplate top, plate bottom, wells, working electrodes, counter electrodes,reference electrodes, dielectric materials, electrical connections, andassay reagents. The wells of the plate may be defined by holes oropenings in the plate top, or as indentations or dimples on a surface ofa plate. The plates may have any number of wells of any size or shape,arranged in any pattern or configuration and can be composed of avariety of different materials. Exemplary embodiments of consumablesthat may be used in the present invention include industry standardformats for the number, size, shape and configuration of the plate andwells, e.g., 96-, 384-, and 1536-well plates, with the wells configuredin two-dimensional arrays. Other formats may include single well plates,2-well plates, 6-well plates, 24-well plates, and 6144-well plates.Multi-well assay plates may be used once or may be used multiple timesand are well suited to applications where the plates are disposable.Various configurations for suitable assay plates may be used in thepresent invention, including but not limited to those depicted in FIGS.11A, 12A, 13A, 13B, 14A, 15, and 16A of U.S. Application Ser. No.2004/0022677, each of which are incorporated herein by reference. Asstated above, the specific configuration and identity of assay testsites, domains, and/or sectors of an assay consumable may be included inthe information saved to the assay consumable identifier.

In this embodiment, the assay consumables may be used in a reader thatcan be used to induce and measure luminescence, e.g., electrode inducedluminescence or electrochemiluminescence, in assays conducted in or onassay consumables, e.g., multi-well assay plates. The accompanying assaysystem can also induce and/or measure current and/or voltage, forexample, at an electrode. The assay system may incorporate, for example,one or more photodetectors; a light tight enclosure; mechanisms totransport the assay plates into and out of the reader (and inparticular, into and out of a light tight enclosure); mechanisms toalign and orient the assay plates with the photodetector(s) and/or withelectrical contacts; additional mechanisms to track and identify plates(e.g. bar code readers); mechanisms to make electrical connections toplates, one or more sources of electrical energy for inducingluminescence, and appropriate devices, electronics and/or software. Theassay reader may also include mechanisms to store, stack, move and/ordistribute one or more multi-well assay plates (e.g. plate stackersand/or plate conveyors). The assay system may be configured to measurelight from multi-well assay plates by measuring light sequentially froma plurality of sectors or regions of the plate (i.e., a grouping of aplurality of adjacent assay domains within a plate) and/or from theentire plate substantially simultaneously or simultaneously. The assaysystem may also incorporate additional microprocessors and computers tocontrol certain functions within the system and to aid in the storage,analysis and presentation of data. Various configurations for suitableassay systems may be used in the present invention, including but notlimited to those depicted in FIGS. 17 to 23 of U.S. Application Ser. No.2004/0022677, each of which are incorporated herein by reference.

The additional microprocessors and computers in the assay system mayalso interact with the assay consumable identifier microprocessor orcontrollers by transferring data and commands to/from the identifier tothe various microprocessors/controllers throughout the system to performvarious operations of the components listed above within the assaysystem.

One assay procedure using an assay consumable, e.g., a multi-domainmulti-well plate, and an assay system would comprise inserting theconsumable in the system to allow the identifier controller to interactwith the identifier affixed to or associated with the consumable.Alternatively, the consumable packaging includes the identifier affixedthereto or associated therewith and before the consumable is insertedinto the system, the identifier associated with the consumable packagingis contacted with the identifier controller. The system may adjust theassay parameters prior to initiating an assay based on the assayinformation saved to the identifier. Thereafter, the system makes theappropriate electrical, fluidic and/or optical connections to theconsumable (making use of electrical, fluidic and/or optical connectorson the consumable and system) and conducts an assay using theconsumable. The sample may be introduced into the consumable prior toinserting the consumable in the system. Alternatively, the sample isintroduced by a component of the system after the consumable is insertedin the system. The assay may also involve adding one or more assayreagents to the consumable and instructions for adding those variousassay reagents may be saved to the identifier and the system adds thosereagents to the consumable before or during the assay according to theinstructions saved to the assay consumable identifier.

Alternatively, the assay consumable is a cartridge and the consumablefurther comprises an element selected from one or more fluidiccomponents, one or more detection components, one or more assay cells,reagents for carrying out an assay, working electrodes, counterelectrodes, reference electrodes, dielectric materials, electricalconnections, dried and/or liquid assay reagents, and combinationsthereof. The cartridge may further comprise at least one assay cell thatcomprises a plurality of distinct assay test sites and/or domains, eachof these test sites and/or domains comprising reagents for measuring adifferent analyte.

An example of an assay consumable cartridge that may be used in thepresent invention is described in US Application Ser. No. 2004/0189311,the disclosure of which is incorporated herein by reference in itsentirety. The assay consumable described therein is an assay cartridgethat incorporates one or more fluidic components such as compartments,wells, chambers, fluidic conduits, fluid ports/vents, valves, and thelike and/or one or more detection components such as electrodes,electrode contacts, sensors (e.g. electrochemical sensors, fluidsensors, mass sensors, optical sensors, capacitive sensors, impedancesensors, optical waveguides, etc.), detection windows (e.g. windowsconfigured to allow optical measurements on samples in the cartridgesuch as measurements of absorbance, light scattering, light refraction,light reflection, fluorescence, phosphorescence, chemiluminescence,electrochemiluminescence, etc.), and the like. Such consumables may alsocomprise reagents for carrying out an assay such as binding reagents,detectable labels, sample processing reagents, wash solutions, buffers,etc. The reagents may be present in liquid form, solid form and/orimmobilized on the surface of solid phase supports present in thecartridge. In this embodiment, the consumables include all thecomponents necessary for carrying out an assay. In addition, the assayconsumable is used in connection with a consumable reader adapted toreceive the consumable and carry out certain operations on theconsumable such as controlling fluid movement, supplying power,conducting physical measurements on the cartridge, and the like.

More specifically, such assay consumable cartridges have one or moreassay test sites (e.g., wells, compartments, chambers, conduits, flowcells, etc.) that may include one or more assay domains (e.g., discretelocations on a assay test site surface where an assay reaction occursand/or where an assay dependent signal, such as an electrochemical or anelectrode induced luminescence signal is induced) for carrying out aplurality of assay measurements. In this embodiment, assay domains aresupported on assay electrodes (in one embodiment, an array of assayelectrodes, e.g., a one dimensional array of assay electrodes) so as topermit the conduct of assays based on electrochemical or electrodeinduced luminescence measurements. The assay domains are, optionally,defined by a dielectric layer deposited on the electrodes. In addition,the assay consumables may have one or more attributes that make themsuitable for use in “point of care” clinical measurements, e.g., smallsize, low cost, disposability, multiplexed detection, ease of use, etc.

The assay consumable cartridge may comprise the necessary electroniccomponents and/or active mechanical components for carrying out an assaymeasurement, e.g., one or more sources of electrical energy, ammeters,potentiometers, light detectors, temperature monitors or controllers,pumps, valves, etc. Alternatively, some or all of the electronic and/oractive mechanical components are arranged within a separate assayreader. The reader would also have the appropriate electrical, fluidicand/or optical connections to the assay consumable for carrying out anassay using the consumable. Using such an arrangement, the assayconsumable can be designed to be low cost and disposable while thereader (which holds the more expensive and complex components) isreusable.

An assay procedure using an assay consumable cartridge and an assaysystem, e.g., an assay reader, may include inserting the cartridge inthe reader to allow the identifier controller to interact with theidentifier affixed to or associated with the cartridge. Alternatively,the cartridge packaging includes the identifier affixed thereto orassociated therewith and before the cartridge is inserted into thereader, the identifier of the cartridge packaging is contacted with theidentifier controller. The reader may adjust the assay parameters priorto initiating an assay based on the assay information saved to theidentifier. Thereafter, the reader makes the appropriate electrical,fluidic and/or optical connections to the cartridge (making use ofelectrical, fluidic and/or optical connectors on the cartridge andreader) and conducts an assay in the cartridge. The sample is may beintroduced into the cartridge prior to inserting the cartridge in thereader. The assay may also involve adding one or more assay reagents tothe cartridge and instructions for adding those various assay reagentsmay be saved to the identifier and the reader adds those reagents to thecartridge before or during the assay according to the instructions savedto the assay consumable identifier.

In one embodiment, a cartridge-based biochemical detection system mayinclude a system housing comprising an optical detector wherein thesystem housing is adapted and configured to receive and position theassay consumable and/or the optical detector for processing. The systemmay further comprise support subsystems that may include one or more ofthe following: storage subsystem for storing assay reagents/consumablesand/or waste; sample acquisition/ preprocessing/storage subsystem forsample handling; fluidic handling subsystem for handling the reagents,sample, waste, etc. and for providing fluids to the detection chambervia a fluid inlet line; electrical subsystem for electrically contactingthe cartridge's electrical contacts and supplying electrical energy tothe electrodes; and a control subsystem for controlling and coordinatingoperation of the system and subsystems and for acquiring, processing andstoring the optical detection signal. The information stored to theassay consumable identifier may include information that is used tocontrol or adjust one or more of the assay system components prior toand/or during the conduct of an assay using the assay consumable.

Still further, the assay consumable may be a container holding one ormore assay reagents, including but not limited to one or more buffers,diluents, and/or reagents used by the assay system in the conduct of anassay. The assay consumable identifier may be affixed to the containerand/or affixed to a packaging for the container.

In one embodiment, the assay consumable identifier comprises memory forstoring information related to the consumable, its history and/or itsuse. In one embodiment, the memory is non-volatile memory. Non-volatilememory is computer memory that can retain the stored information withoutpower. Examples of non-volatile memory which may be used in theconsumable identifier include, but are not limited to, electronicnon-volatile memory (e.g., read-only memory and flash memory), magneticmemory (e.g., hard disks, floppy disk drives, and magnetic tape),optical memory (optical disc drives) and hybrids of these approaches(e.g., magneto-optical memory).

In one embodiment, the assay consumable identifier comprises EPROM(erasable programmable read-only memory), a type of programmableread-only memory that can be erased by exposing it to ultraviolet light.Once erased, it can be reprogrammed with new or modified data. Inanother embodiment, the assay consumable identifier comprises EEPROM(electronically erasable programmable read-only memory) a class ofnon-volatile electronic memory that can be electrically erased andreprogrammed without exposure to UV light. An EEPROM can be written toor programmed more than once and can be selectively programmed (the usercan alter the value of certain cells without erasing the programming ofthe other cells). Therefore, sections of data can be erased and replacedwithout needing to alter or reinstall the rest of the chip'sprogramming.

In another embodiment, the assay consumable identifier comprises flashmemory, a specific type of EEPROM that is erased and programmed in largeblocks. Although flash memory is technically a type of EEPROM, the term“EEPROM” is generally used to refer specifically to non-flash EEPROMwhich is erasable in small blocks, typically bytes. Because erase cyclesare slow, the large block sizes used in flash memory erasing give it asignificant speed advantage over conventional EEPROM when writing largeamounts of data.

In another embodiment, the assay consumable identifier comprises a smartcard, chip card, or integrated circuit card (ICC) (referred tocollectively as “ICCs”). These are small cards with embedded integratedcircuits which can process and store data. There are two broadcategories of ICCs; i) “memory cards” that contain non-volatile memorystorage components and, optionally, some specific security logic but donot contain microprocessors and Ii) “microprocessor cards” that combinenon-volatile memory components with microprocessor components and enablethe processing of information being read into or out of the ICC. The ICCelectronic components are supported on a card that is, typically, madeof plastic such as PVC or ABS. The card may include an embedded hologramto avoid counterfeiting. Contact ICCs have conductive contact pads. Wheninserted into a reader, the contact pads on the ICC make contact withelectrical connectors in the reader to allow for transfer of informationbetween the reader and the ICC, for example, allowing the reader toread, erase or write information on the ICC.

Another method of transferring information is via an RFID, i.e., radiofrequency identification, which is similar in theory to bar codeidentification. With RFID, the electromagnetic or electrostatic couplingin the RF portion of the electromagnetic spectrum is used to transmitsignals. An RFID system consists of an antenna and a transceiver, whichread the radio frequency and transfers the information to a processingdevice, and a transponder, or tag, which is an integrated circuitcontaining the RF circuitry and information to be transmitted.

Identification can also be accomplished by reading a bar code. One ofthe key differences between RFID and bar code technology is that RFIDeliminates the need for line-of-sight reading that bar coding dependson. Also, RFID scanning can be done at greater distances than bar codescanning. High frequency RFID systems (850 MHz to 950 MHz and 2.4 GHz to2.5 GHz) offer transmission ranges of more than 90 feet, althoughwavelengths in the 2.4 GHz range are absorbed by water (the human body)and therefore has limitations.

In one embodiment, the non-volatile memory used in the present inventionis selected from the group consisting of an EEPROM, flash memory, ICCand combinations thereof. In one embodiment, the non-volatile memory isan EEPROM. In an alternate embodiment, the non-volatile memory is anRFID.

In an additional alternative embodiment, two or more non-volatile memorycomponents may be used in the present invention. For example, a firstassay consumable comprising a first identifier may be used in the assaysystem, and an additional assay consumable comprising an additionalidentifier may also be used in the assay system. Each identifier mayinclude the same or different type of memory. However, for eachdifferent form of memory, there will be a separate identifiercontroller. And certain assay information may be stored on oneidentifier and other assay information on an additional identifier ofthe same or different type. For example, one assay consumable used inthe system may comprise an EEPROM or RFID as an identifier, whereas thesystem may also use an additional assay consumable comprising, e.g., abar code as a identifier. The assay system would comprise an identifiercontroller capable of interfacing with the first identifier, i.e., theEEPROM or RFID, and the system will further comprise an additionalcontroller that will interface with the bar code.

The assay system of the present invention includes an identifiercontroller that controls the operation of the non-volatile memory andother components of the assay system. The identifier controlleroptionally includes a micro-controller to interface with thenon-volatile memory over a communication interface, which mayincorporate conventional interface architectures and protocols such asI²C, a two line serial bus protocol. The microcontroller addresses thenon-volatile memory and performs write, read and erase operations on thememory.

The consumable identifier may be located on the consumable or it may bea separate component. In either case, the system may be designed to havea unique identifier for each consumable. Alternatively, the system maybe configured so that one separate consumable identifier is used to holdinformation relating to a plurality of consumables. In one example, eachpackage of consumables has a package-specific identifier mounted on thepackage (or, alternatively, supplied in the package) that holdsinformation relating to the plurality of consumables in the package.Optionally, each consumable also carries an additional uniqueconsumable-specific identifier attached to the consumable. Thisconsumable-specific identifier is used primarily to uniquely identifythe consumable and link it to information on the package-specificidentifier. In this embodiment, lot information content and/ornon-editable identifiers such as bar codes may be used.

The various components of the assay system may be housed together in asingle unit or may be housed separately. For example, the assay systemmay include an assay reader and an identifier controller as separateunits. The assay system provides for communication (which may be wiredor wireless communication) directly between the assay reader andidentifier controller or, alternately, indirectly through additionalcomponents of the assay system. In an alternative embodiment, theidentifier controller is housed within the assay reader. In such anembodiment, the assay reader may be configured such that insertion ofthe consumable into the reader during the conduct of an assay alsoenables communication between the consumable identifier and theidentifier controller (e.g., a port into which the consumable isinserted includes components for processing and/or reading theconsumable and also includes components, such as electrical contacts ora radio transmitter, for communicating with the consumable identifier).In one example, when the consumable is loaded into the assay system,electrical contacts are made between the controller and the identifier,e.g., non-volatile memory. The controller is then able to read, eraseand/or write assay information to the identifier. Alternatively, theassay reader may have separate ports for processing/reading a cartridgeand for communicating with the consumable identifier. The user placesthe assay consumable or packaging in or in proximity to the controllerport such that the controller makes electrical contact with theidentifier to enable the controller to read, erase and/or write assayinformation to the non-volatile memory

In one embodiment, the identifier comprises non-volatile memory selectedfrom the group consisting of an RFID tag, a bar code, an EPROM, andEEPROM. Still further, the identifier may comprise an EEPROM selectedfrom the group consisting of flash memory and ICC.

The identifier is programmed, e.g., during the manufacturing process orat another time prior to use in the assay system. The identifier may beprogrammed with information (referred to herein as “assay information”)which is used before, during or after an assay or a step of a multi-stepassay to control the operation of the assay system, reader or acomponent of the assay system. The term “assay information” may includeany information used to uniquely identify a particular assay or assaystep, assay consumable, consumable domain(s), biological reagent orsample or to distinguish a particular assay, assay step, assayconsumable, consumable domain(s), biological reagent or sample fromother assay consumables, consumable domains, biological reagents orsamples. Assay information may include consumable information, sampleinformation, chain of custody information, consumable/test siteinformation, assay process information, consumable security information,and combinations thereof. Each type of assay information is described inmore detail below.

For example, the assay information may include consumable informationthat includes but is not limited to lot identification information, lotspecific analysis parameters, manufacturing process information, rawmaterials information, expiration date, Material Safety Data Sheet(MSDS) information, product insert information (i.e., any informationthat might be included or described in a product insert that wouldaccompany the assay consumable, e.g., the assay type, how the assay isperformed, directions for use of the assay consumable, assay reagents,or both, etc.), threshold and/or calibration data for one or morereagents used in the assay consumable or in an assay or a step of amulti-step assay, and the location of individual assay reagents and/orsamples within one or more test sites of the assay consumable.

The consumable identifier may also include lot identificationinformation, i.e., information that is used to identify a particular lotof assay consumables, which is distinct from lot-specific analysisparameters, which includes that information that is unique to a givenlot that may be used by the system, e.g., to conduct an assay with aconsumable from that lot or to analyze assay results derived from aconsumable from that lot. In one embodiment, if the assay consumable isa multi-well assay plate or a cartridge, the lot-specific analysisparameters may include, but are not limited to, the following: (i) therevision level that determines the schema used to interpret theinformation; (ii) the consumable type; (iii) the date of manufacture;(iv) the lot number; (v) the date of expiration; (vi) a cross-talkcorrection matrix, to account for chemical cross-reactivity; (vii) athreshold for assays to be conducted in the consumable and each internalnegative control; (viii) a range for each internal positive control;(ix) ranges for each assay to be conducted in the cartridge for thepositive control sample; (x) a software checksum to ensure integrity ofthe data; (xi) in-well (or in-test site) control acceptance ranges;(xii) assay names and/or identifiers; (xiii) information concerningassay quality control, including negative and positive quality controlmaterials that are used to verify the operation of the reader and theconsumable; (xiv) calibration information such as a master calibrationcurve; and (xv) number and names of assay calibrators and/or assaycalibrator acceptance ranges.

The assay information may include sample information, such as thelocation of samples within at least one test site of the assayconsumable, assay results obtained on said assay consumable for thesample, and the identify of samples that have been and/or will be assayin the assay consumable.

The assay information may also relate to chain of custody, e.g.,information regarding the control, transfer and/or analysis of thesample and/or an assay consumable. Chain of custody information may beselected from user identification, sample identification, time and datestamp for an assay, the location of the assay system in a laboratoryduring the assay, calibration and QC (quality control) status of theassay system during the assay, custody and/or location information forthe assay consumable before and after the conduct of the assay, assayresults for a given sample, as well as user created free text commentsinput before, during or after an assay is processed by the system. Stillfurther, chain of custody information may include time, date,manufacturing personnel or processing parameters for one or more stepsduring the manufacture of the assay consumable, custody, location and/orstorage conditions for the assay consumable following manufacture and/orbetween steps during the manufacture of the assay consumable.

Assay information may also include consumable/test site information,such as consumable type and structure, the location and identity (e.g.,the structure, composition, sequence, concentration and/or origin) ofassay reagents included within an assay consumable, and the location andidentity of assay reagents within an assay test site of the assayconsumable.

In addition, the assay information may include assay process informationconcerning the individual assay parameters that should be applied by thesystem or reader during the assay. For example, such assay informationmay include a sequence of steps for a given assay, the identity,concentration and/or quantity of assay reagents that should be used oradded during the assay or during a particular step of an assay, e.g.,buffers, diluents, and/or calibrators that should be used in that assay.In addition, the assay information may include data regarding how one ormore steps in an assay protocol (e.g., dilution or reagent additionsteps) may be adjusted to account for lot to lot or consumable toconsumable differences. The amount of diluent added and/or the nature ofthe diluent may be altered based on such differences. Similarly, theamount of a given reagent that may be added during the conduct of anassay, an incubation period and/or temperature for one or more steps ofan assay may also be dependent on lot to lot or consumable to consumabledifferences.

The assay information may also include the type or wavelength of lightthat should be applied and/or measured by the system or reader duringthe assay or a particular step of a multi-step assay; the temperaturethat should be applied by the system or reader during the assay; theincubation time for an assay; and statistical or other analyticalmethods that should be applied by the system or reader to the raw datacollected during the assay.

In an additional embodiment, the information includes consumable/testsite information i.e., information concerning assays previouslyperformed by a reader on one or more test sites of the consumable, andinformation concerning assays to be performed by a reader on one or moretest sites within the consumable. Therefore, once the assay is conductedby the system, the controller may be used to write the results of theassay to the identifier. Such information includes, but is not limitedto raw or analyzed data collected by the system during the assay(wherein analyzed data is data that has been subjected to statisticalanalysis after collection and raw data is data that has not beensubjected to such statistical analysis), a list of test sites and/ordomains within the assay consumable used during a given assay, aschedule of events to be conducted on an assay consumable or a test siteand/or domain within an assay consumable, a list of those test sitesand/or domains of the assay device that have not be subjected to anassay, assay or system errors that resulted during a given assay orassay step, and combinations thereof.

Moreover, the information comprises data that directly or indirectlycontrols a component of the assay system, e.g., one or morephotodetectors, a light tight enclosure; mechanisms to transport theassay consumables into and out of the reader; mechanisms to align andorient the assay consumables with the one or more photodetector(s)and/or with electrical contacts in the reader; additional mechanismsand/or data storage media to track and/or identify assay consumables;one or more sources of electrical energy to induce luminescence;mechanisms to store, stack, move and/or distribute one or moreconsumables; mechanisms to measure light from a consumable during theassay sequentially, substantially simultaneously or simultaneously froma plurality of test sites of the consumable; and combinations thereof.

Still further, the identifier/controller in the assay system may be usedas a security mechanism, e.g., to confirm that the correct assayconsumable is being used in the system (referred to herein as“consumable security information”). The assay information may include adigital signature to prove that the consumable was manufactured by thedesignated vendor. In one embodiment, if an inappropriate assayconsumable is present in the system, e.g., a counterfeit consumable or aconsumable that is otherwise incompatible with the assay system, thecontroller will disable the system, reader or a component thereof. Inaddition or alternatively, the identifier/controller may be used todetect the proper placement of the assay consumable in the system, e.g.,the proper orientation of the assay consumable or a portion thereof, inthe assay system, such that the controller will disable the system,reader or a component thereof until the assay consumable is placed inthe correct orientation. Still further, the identifier/controller in thesystem may also be used to detect a defect in the assay consumable or anassay test site and/or domain and the controller will disable thesystem, reader or a component thereof accordingly. For example,depending on the nature of the defect in the assay consumable or domain,the controller may disallow the use of the assay consumable in itsentirety or direct the reader to disallow the use of a test site and/ordomain or a set of test site and/or domain in the assay consumable. Inone embodiment, the reader may perform a diagnostic analysis on theassay consumable and/or a test site and/or domain therein to identifydefects therein and the controller will write the results of thatdiagnostic analysis to the identifier on the consumable. If theconsumable is later used in a different reader, the results of thisdiagnostic analysis will be read by the controller and used by thereader to adjust the use of that consumable or a test site and/or domainin that consumable accordingly. In a further embodiment, the assayconsumable may be subjected to a quality control process during or afterits manufacture and the results of that quality control analysis may bewritten to the identifier for later use and/or verification by the userof the assay consumable in an assay reader.

The assay information may also include authorization information forconsumables or test site and/or domain thereof or biological reagents,such as information regarding whether a particular user has a validlicense to use a particular consumable or biological reagent, includingthe number of times the user is permitted to use the particularconsumable or biological reagent in a particular assay and thelimitations, if any, on that use, e.g., whether the user's license isfor research purposes only. Such information can also include validationinformation regarding whether a particular consumable or biologicalreagent has been subject to a recall or has otherwise become unsuitableor unauthorized for use. The recall information and an optional lastrecall check date and/or timestamp can be written to the identifier.

The assay information may further include information regarding theorigin of a biological reagent used in an assay consumable, test siteand/or domain, including for example an identification of an originalsample from which it was derived or the number of generations removed itis from an original sample. For example, if an assay reagent used in anassay is an antibody, the assay information may include theidentification of the hybridoma from which the antibody was derived,e.g., the ATCC accession number for that hybridoma.

The assay information may additionally include information regarding aconsumable, test site, domain, sector, or a biological reagent or sampleas individual operations are performed on that consumable, test site,domain, sector, or biological reagent or sample, for example duringmanufacture of the consumable, test site, domain, sector, or biologicalreagent or while an assay or step is being performed on the consumable,test site, domain, sector, or biological reagent or sample. For example,if an assay consumable includes a plurality of assay test sites,domains, and/or sectors, the assay system may perform an assay or stepof a multi-step assay on a single test site, domain and/or sector of theassay consumable. Once that assay or assay step is completed by theassay system, the controller records the results of that assay, e.g.,the raw or analyzed data generated during the assay or assay step, tothe identifier, and/or the controller records which test site, domainand/or sector of the assay consumable were used during the assay orassay step and/or which test site, domain and/or sector of the assayconsumable have yet to be used. The assay consumable may be stored forlater use and when the user is ready to use another test site, domainand/or sector of the assay consumable, the controller reads the assayinformation stored on the identifier of the assay consumable to identifywhich test site, domain and/or sector has been used, has yet to be used,and/or the results of those assays. The controller may then instruct theassay system, reader or component thereof to conduct an assay or assaystep on an unused test site, domain and/or sector.

In addition, a given assay protocol may require a set of consumables ofa particular type. Therefore, if the user inputs a specific type ofassay consumable, e.g., a multi-well assay plate, for use in aparticular assay protocol, one or more additional assay consumables maybe required to carry out that assay protocol in the system, e.g., one ormore reagents may be required for use with that multi-well assay plate.Each of the required consumables may include a consumable identifierwith information concerning the consumable requirements for an assayprotocol. When one of the required consumables is input into the assaysystem and the identifier controller interacts with the consumableidentifier for that consumable, the system will take an inventory of thecomponents present in the system and compare the results to theconsumable requirements stored to the consumable identifier. If anyrequired consumables are not present or are present in insufficientsupply, the system will prompt the user to input the additional requiredconsumables for that assay protocol based on the information stored onthe required consumable identifier. If two or more assay consumables areused in the system, the instrument will correctly identify a first assayconsumable and any associated consumables based on the consumablerequirements stored to the identifiers associated with each consumable.The system will verify that the assay consumable and associatedconsumables are loaded on the system before the sample is run. In thecase where only the first assay consumable is loaded into the systemwithout the corresponding associated consumable, the system will promptthe user to load the associated consumable if the instrument does notidentify the associated consumable within the system within a predefinedperiod of time. The system will notify the user if mismatched assayconsumables are loaded on the instrument. The system will not runsamples if there are no available matched sets of assay consumables(e.g., multi-well assay plates and given reagents for a particularassay). The system will check for assay consumable expiration prior tothe start of an assay and the system will alert the user and prevent theuse of an expired consumable. The system will not process a sample ifthe consumables have expired prior to sample aspiration. If a partiallyused assay consumable is installed into a different instrument,consumable usage will automatically start with the next available unusedwell.

The identifier may also be used to track the time a given assayconsumable is present in the assay system. Therefore, when an assayconsumable is inserted into or contacted with an assay system, a timeris initiated in the assay system and the start time is recorded to theidentifier. When the assay is initiated by the system on the consumableor a test site, domain and/or sector within the consumable, the time isalso recorded to the identifier. If the instrument, system or acomponent thereof is shutdown (e.g., by turning the power off), thetimer is stopped and that time is recorded to the identifier. Thus,whenever the timer is stopped, the accumulated onboard time is recordedto the identifier.

According to various embodiments, biological samples or reagents thatare provided in the carriers described above are licensed separatelyfrom systems designed to operate on the biological reagents. In variousembodiments the assay system, reader or a component thereof is coupledto a network that allows the system to communicate over public and/orprivate networks with computer systems that are operated by or on behalfof the users, manufacturers and/or licensors of the biological reagents,consumables or systems. In various embodiments, a limited license canprovide for the use of licensed biological reagents, consumables orsystems for a particular biological analysis on only licensed systems.Accordingly, a system can authenticate a biological reagent, consumableor system based on, for example, a digital signature contained in theidentifier associated with a particular consumable, if a particular userhas a valid license. In various embodiments, the identifier can also beprogrammed to provide for a one time use such that biological reagentscannot be refilled for use with the same authentication.

In certain embodiments, when the identifier is read by a system, readeror component thereof that has access to a public or private data networkoperated by or on behalf of the users, manufacturers and/or licensors ofthe biological reagents, consumables or systems, certain assayinformation may be communicated to the assay system and read, write orerased locally via the identifier/controller on the assay system. Forexample, recall and/or license information may be a subset of assayinformation that is available via the network connections, whereasadditional assay information e.g., lot-specific, expiration date,calibration data, consumable specific information, assay domaininformation, assay results information, consumable security information,or combinations thereof, may be stored locally on the identifier andotherwise unavailable via the network connections on the assay system.In one embodiment, recall, license and/or consumable securityinformation may be available via the network connections on the assaysystem and the remaining assay information is stored locally on theidentifier. The assay system or reader includes system hardware, systemfirmware, system data acquisition and control software, and method orconsumable data. In various embodiments, the system hardware includeselectronic control and data processing circuitry, such as amicroprocessor or microcontroller, memory, and non-volatile storage. Invarious embodiments, the system hardware also includes physical devicesto manipulate biological reagents such as robotics and sample pumps. Invarious embodiments, the system firmware includes low-level,computer-readable instructions for carrying out basic operations inconnection with the system hardware. In various embodiments, the systemfirmware includes microprocessor instructions for initializingoperations on a microprocessor in the system hardware.

The system data acquisition and control software is higher-levelsoftware that interfaces with the system firmware to control the systemhardware for more specific operations such as operating a charge coupleddevice (CCD) to acquire visual luminescence information regarding aparticular biological analysis. In various embodiments the dataacquisition and control software includes a software-implemented statemachine providing, for example, the following states: (i) idle; (ii)running; (iii) paused; and (iv) error. In various embodiments, when thestate machine is in the idle state, it can receive an instruction fromthe general purpose machine to perform a particular data acquisition orsystem control operation. In various embodiments, the general purposecomputer opens a TCP/IP socket connection to the system, determineswhether the system is in the idle state and then begins transmittinginstructions and/or parameters. In various embodiments, an encryptedTCP/IP connection is established, using, for example, the SSH protocol.The instructions and/or parameters can be in the form of ASCII encoded,human readable consumable and/or method information that defines thebehavior of the biological system. In various embodiments, theconsumables and/or methods are stored in the form of ASCII text files.In various embodiments, the general purpose computer uses the FTPprotocol to transfer the ASCII text files to the system. In variousother embodiments the method and/or consumable information is stored inand read from the identifier. The method and/or consumable informationcan be stored in the form of an ASCII text file in the identifier, butit is understood that the information can be represented in other dataformats without departing from the present teachings.

According to various embodiments, the consumable, macro, and/or methodinformation includes parameters that can be used by the system dataacquisition and control software to perform specific data acquisitionand system control operations. In various embodiments, the method and/orconsumable information contains sequences of operations to be performedby the system or control parameters for use in connection with the dataacquisition or control software. In one specific embodiment, the assayconsumable is a cartridge as described herein above. The cartridge isprovided with a consumable identifier, e.g., a memory card (which issupplied with the packaging for the cartridge or a set of a plurality ofcartridges) that includes assay information, e.g., lot informationand/or lot specific parameters. Prior to running an assay using acartridge from a new lot of cartridges, the user inserts the memory cardinto the reader and uploads the assay information to the reader'sinternal memory. The cartridge also includes an additional consumableidentifier, e.g., a bar code, with the cartridge lot identifier storedthereon. At the beginning of an assay, the reader loads the cartridgeand reads the cartridge lot identifier from the cartridge barcode usingits internal barcode reader. The reader determines if it has lotspecific information stored for that lot identifier. Then the readerreads the expiration date from the lot-specific parameters stored in itsinternal memory and rejects the cartridge if the on-board clock is pastthe expiration date. The reader executes the assay protocol anddetermines results based on the lot specific parameters.

In an alternate embodiment, the assay system uses a plurality ofdifferent assay consumables, e.g., one or more multi-well assay plates,one or more sample tube racks, and/or containers for assay reagents.Certain of the consumables used in the system may be associated with anidentifier and others may not. In one embodiment, each consumable isassociated with an identifier. In one specific embodiment of theinvention, an assay consumable used in the system includes an EEPROM orRFID as a consumable identifier and the assay system includes acorresponding EEPROM or RFID controller. The controller detects anduploads the data stored on the identifier and the system optionallyadjusts one or more assay parameters based on the data uploaded from theidentifier. Once the assay is completed, the identifier controllerwrites information to the identifier concerning that assay or the use ofthat consumable in the system. The instrument is programmed to rejectany consumable that does not have a readable identifier.

The system will prompt the user to scan the reagent identifiers and willrecord the scanned information. The system will also prompt the user toscan the controls, calibrator and reagent identifiers and record thescanned information. The system will persistently track the consumablestate so that state can be maintained in the case of a power loss orunexpected shutdown. The system will estimate the volume of fluids inthe reagent bottles and it will estimate reagent consumption. The systemwill record the user identification for the user and that assayinformation will be written to the identifier. The system will alsorecord/read the timestamp when an assay is run to the identifier and itwill allow the user to enter and modify a free text comment before,during or after the assay is processed, which is also written to theidentifier. The user will input sample identification for each sampleand that assay information is also written to the identifier.

In a further embodiment, the assay system uses a plurality of differentassay consumables, e.g., one or more multi-well assay plates, one ormore sample tube racks, and/or containers for assay reagents. A singleassay consumable used in the system may include a plurality ofconsumable identifiers, e.g., a first identifier that includesinformation that pertains to the entire consumable and one or moreadditional consumable identifiers of the same or different type thatincludes information that pertains to a component of that consumable.For example, if the assay consumable is a sample tube rack, theconsumable includes an EEPROM or RFID with information specific for theentire rack, e.g., lot information and/or lot specific parameters forthe rack. The sample tube rack may also include two or more additionalidentifiers, e.g., a barcode, with information specific for individualsamples and/or positions within the rack, e.g., information concerningthe sample present at a given position in the rack. In addition, theadditional identifier may be used by the system to identify the presenceor absence of a sample or reagent in a given position within the rack,e.g., if the additional identifier is obscured and cannot be read by thesystem, the sample or reagent is present in the rack and if theadditional identifier is read by the system, the sample or reagent isnot present.

For each type of consumable identifier used by the assay system there isa corresponding identifier controller. For example, if the system uses amulti-well assay plate with an EEPROM identifier and a container forassay reagents with a barcode, then the system will include an EEPROMcontroller and a barcode controller. Each controller detects and uploadsthe data stored on a given identifier and the system optionally adjustsone or more assay parameters based on the data uploaded from thatidentifier. Once the assay is completed, the identifier controllerwrites information to the identifier concerning that assay or the use ofthat consumable in the system. The instrument is programmed to rejectany consumable that does not have a readable identifier.

The system will prompt the user to scan the reagent identifiers and willrecord the scanned information. The system will prompt the user to scanthe controls, calibrator and reagent identifiers and record the scannedinformation. The system will persistently track the consumable state sothat state can be maintained in the case of a power loss or unexpectedshutdown. The system will estimate the volume of fluids in the reagentbottles and it will estimate reagent consumption.

In one specific embodiment, the invention provides an assay systemconfigured to use an assay cartridge in the conduct of an assay, whereinthe assay system comprises a reader adapted to perform the followingoperations (i) reading cartridge lot identification information from afirst consumable identifier associated with the assay consumable; (ii)reading lot specific parameters from an additional consumableidentifier; (iii) using the lot identification information and the lotspecific parameters to adjust one or more operations performed by theassay system before, during and/or after the conduct of an assay by thesystem. In this embodiment, the lot specific parameters are selectedfrom the group consisting of (i) a revision level that determines schemaused to interpret assay results and/or assay information; (ii) cartridgetype; (iii) year of cartridge manufacture; (iv) cartridge lot number;(v) expiration date of cartridge and/or reagents used in the assay; (vi)a cross-talk correction matrix to account for chemical cross-reactivity;(vi) threshold values for assays to be conducted in the cartridge; (vii)a range for internal positive control(s) used in the assay; (viii) aranges for each assay to be conducted in the cartridge for a positivecontrol sample; and (ix) a software checksum. The first consumableidentifier comprises non-volatile memory, e.g., an RFID tag, a bar code,ICC, an EPROM, and EEPROM. In one embodiment, the non-volatile memory isa bar code. The additional consumable identifier also comprisesnon-volatile memory, e.g., an RFID tag, a bar code, ICC, an EPROM, andEEPROM. In one embodiment, the additional consumable identifier is anICC, e.g., a memory card.

Therefore, an assay procedure using an assay consumable cartridge in anassay system, e.g., an assay reader, includes inserting the cartridge inthe reader to allow the identifier controller to interact with theidentifier affixed to or associated with the cartridge. Alternatively,the cartridge packaging includes the identifier affixed thereto orassociated therewith and before the cartridge is inserted into thereader, the identifier of the cartridge packaging is contacted with theidentifier controller. The identifier controller associated with thereader reads the cartridge lot identification information from the firstconsumable identifier as well as the lot specific parameters from anyadditional consumable identifier. The reader then uses the lotidentification information and the lot specific parameters to adjust oneor more operations performed by the reader before, during and/or afterthe conduct of an assay. For each lot specific parameter, the reader mayadjust the system or output accordingly. Thereafter, the reader makesthe appropriate electrical, fluidic and/or optical connections to thecartridge (making use of electrical, fluidic and/or optical connectorson the cartridge and reader) and conducts an assay in the cartridge. Thesample may be introduced into the cartridge prior to inserting thecartridge in the reader. The assay may also involve adding one or moreassay reagents to the cartridge and instructions for adding thosevarious assay reagents may be saved to the identifier and the readeradds those reagents to the cartridge before or during the assayaccording to the instructions saved to the assay consumable identifier.

In another specific embodiment, the invention provides an assay systemconfigured to use a multi-well assay plate, an additional multi-wellassay plate (referred to as an auxiliary plate), and one or more sampletube racks in the conduct of an assay, wherein the assay systemcomprises a reader adapted to perform one or more of the followingoperations (i) reading tube position information from a first consumableidentifier associated with the one or more sample tube racks; (ii)reading assay information and lot specific parameters from an additionalconsumable identifier associated with the auxiliary plate; (iii) usingposition information and lot specific parameters to adjust one or moreoperations performed by the assay system before, during and/or after theconduct of an assay using the multi-well assay plate and the auxiliaryplate; (iv) erasing information from a consumable identifier; and (v)writing information to a consumable identifier. In one embodiment, theassay information is selected from the group consisting of (i) a digitalsignature to verify manufacturer identify; (ii) lot code of themulti-well assay plate and/or the auxiliary plate; (iii) expiration dateof the multi-well assay plate and/or the auxiliary plate; (iv) type ofmulti-well assay plate and/or the auxiliary plate; (v) serializedidentification for the auxiliary plate; and (vi) lot specific parametersfor the multi-well assay plate and/or the auxiliary plate. Stillfurther, the lot specific parameters for the multi-well assay plate areselected from the group consisting of (i) in-well control acceptanceranges; (ii) assay names; (iii) assay identifiers; (iv) assaythresholds; (v) number and identity of assay quality controls; (vi)assay quality control acceptance ranges; (vii) calibration information;(viii) number and identity of assay calibrators; (ix) assay calibratoracceptance ranges; (x) chemical cross-talk matrix for the multi-wellassay plate; and (xi) combinations thereof. The first consumableidentifier may comprise non-volatile memory, e.g., an RFID tag, a barcode, ICC, an EPROM, and EEPROM. In one embodiment, the non-volatilememory is a bar code. The additional consumable identifier comprisesnon-volatile memory, e.g., an RFID tag, a bar code, ICC, an EPROM, andEEPROM. In one embodiment, the additional consumable identifier is anEEPROM or an RFID.

Reference is made to copending U.S. Provisional Patent Application Ser.No. 61/271,874, filed Jul. 27, 2009 (docket number 120000USPR00), thedisclosure of which is incorporated herein by reference. In oneembodiment, a method of using such an assay system includes (a)introducing a sample tube rack into a sample rack subassembly; (b)reading sample and assay-specific information from the identifiers onthe sample rack subassembly and/or reading sample and assay-specificinformation manually input into the computer user interface by the user;(c) introducing an auxiliary plate to an auxiliary plate subassembly;(d) reading assay-specific information from the identifiers on theauxiliary plate; (e) introducing an assay test plate into a plateintroduction aperture of a light-tight enclosure of the apparatus; (f)reading assay-specific information from the identifiers on the assaytest plate; (g) sealing the door of the plate introduction aperture, (f)translating the test plate to position one or more wells under a lightdetector, (g) rehydrating reagents in one or more auxiliary wells of theauxiliary plate using a pipetting arm subassembly and/or pretreating oneor more wells of the test plate using the pipetting arm subassembly; (h)collecting a sample volume from a sample tube of the sample racksubassembly and pipetting that sample volume into a well of an assaytest plate; (i) collecting sample reagents from the auxiliary plate anddispensing those reagents into a well of the assay test plate; (j)detecting luminescence from the one or more wells, (k) repeating one ormore of the preceding steps on additional wells of the test plate, usingadditional auxiliary wells of the auxiliary plate; (j) translating theused test plate to a plate elevator; (k) raising the plate elevator; and(l) removing the test plate from the plate introduction aperture.

The method may also, optionally, comprise one or more of: i)pre-treating sample and/or reagent in a auxiliary well of the auxiliaryplate and pipetting that pre-treated sample and/or reagent into or outof one of a auxiliary well of a test plate; ii) removing seals from oneor more of the auxiliary wells and/or wells of the auxiliary plateand/or test plate, respectively, or iii) applying electrical energy toelectrodes in one or more of said test plate wells (e.g., to induceelectrochemiluminescence).

One assay procedure using an assay consumable, e.g., a multi-domainmulti-well plate, and an assay system would comprise inserting theconsumable in the system to allow the identifier controller to interactwith the identifier affixed to or associated with the consumable.Alternatively, the consumable packaging includes the identifier affixedthereto or associated therewith and before the consumable is insertedinto the system, the identifier associated with the consumable packagingis contacted with the identifier controller. The system may adjust theassay parameters prior to initiating an assay based on the assayinformation saved to the identifier. Thereafter, the system makes theappropriate electrical, fluidic and/or optical connections to theconsumable (making use of electrical, fluidic and/or optical connectorson the consumable and system) and conducts an assay using theconsumable. The sample may be introduced into the consumable prior toinserting the consumable in the system. Alternatively, the sample isintroduced by a component of the system after the consumable is insertedin the system. The assay may also involve adding one or more assayreagents to the consumable and instructions for adding those variousassay reagents may be saved to the identifier and the system adds thosereagents to the consumable before or during the assay according to theinstructions saved to the assay consumable identifier.

The present invention is not to be limited in scope by the specificembodiments described herein. Indeed, various modifications of theinvention in addition to those described herein will become apparent tothose skilled in the art from the foregoing description and accompanyingfigures. Such modifications are intended to fall within the scope of theclaims. Various publications are cited herein, the disclosures of whichare incorporated by reference in their entireties.

What is claimed is:
 1. A method of using an assay consumable in an assaysystem, wherein said assay consumable comprises a consumable identifierand said assay system comprises a reader adapted to perform an operationselected from the group consisting of (i) read information from saidconsumable identifier; (ii) erase information from said consumableidentifier; (iii) write information to said consumable identifier; and(iv) combinations thereof, said method comprising the steps of (a)reading information from said consumable identifier; (b)conducting anassay in said assay system using said assay consumable; (c) writinginformation resulting from said assay conducted in step (b) to saidconsumable identifier; and (d) tracking use of said assay consumable. 2.A method of tracking use of an assay consumable comprising an assayconsumable identifier and a plurality of test sites, said methodcomprising (a) reading test site usage information from said assayconsumable identifier; (b) identifying, based on said test site usageinformation, an available test site on said consumable; (c) carrying outan assay using said available test site; and (d) writing updated testsite usage information to said assay identifier.
 3. The method of claim2 wherein said information is selected from the group consisting ofchain of custody information; assay results obtained on said assayconsumable or one or more test site(s); identity of samples that havebeen and/or will be assayed in said assay consumable or a portionthereof.
 4. The method of claim 3 wherein said information is chain ofcustody information comprising information regarding the control,transfer and/or analysis of said sample.
 5. The assay system of claim 3wherein said information is chain of custody information comprisinginformation regarding the control, transfer and/or manufacture of saidassay consumable.
 6. The assay system of claim 3, wherein said chain ofcustody information is selected from the group consisting of useridentification; time and date stamp for said assay; location of saidassay system during said assay; calibration and QC status of said assaysystem during said assay, custody and/or location information for saidassay consumable before and after the conduct of said assay; assayresults for said sample; and combinations thereof.
 7. The assay systemof claim 3, wherein said information is chain of custody informationselected from the group consisting of time, date, manufacturingpersonnel or processing parameters for one or more steps during themanufacture of said assay consumable; custody, location and or storageconditions for said assay consumable following manufacture and/orbetweens steps during the manufacture of said assay consumable; andcombinations thereof.
 8. A method of tracking the manufacture of anassay consumable, wherein said assay consumable comprises an identifierand one or more component parts and said manufacturing process includesone or more operations conducted by one or more manufacturingconsumables each comprising a reader adapted to perform an operationselected from the group consisting of (i) reading manufacturinginformation from said identifier; (ii) erasing manufacturing informationfrom said identifier; (iii) writing manufacturing information to saididentifier; and (iv) combinations thereof; said method comprising (a)affixing said identifier to a first component of said consumable; (b)performing an operation of said manufacturing process; (c) writingmanufacturing information to said identifier, wherein said manufacturinginformation comprises information related to the operation performed instep (b); (d) performing an additional step in said manufacturingprocess; and (e) writing manufacturing information to said identifier,wherein said manufacturing information comprises information related tothe operation performed in step (d).
 9. The method of claim 8 whereinsaid manufacturing information is selected from the group consisting oflot-specific information; reagent expiration date; calibration data;threshold information; the location of individual reagents within a testsite of the assay consumable; chain of custody information; andcombinations thereof.